Profound hearing impairment occurs in approximately one in 1000 children at birth, primarily due to genetic causes. In cultures with a tradition of consanguinity, rates of congenital hereditary hearing impairment may be much higher. Palestine is such a culture, and in some locales, more than 10 percent of children are born deaf. Of the many genes likely to be involved in hereditary hearing impairment, 62 have been mapped and 15 cloned so far. Normal counterparts of these genes must be critical to normal development of hearing. Therefore, identifying genes for hereditary hearing impairment and characterizing their normal functions offers a powerful approach for developing treatments for sensorineural deafness, both in children and among older adults. Extended kindreds with rigorously diagnosed hearing impairment and carefully constructed genealogies, who are enthusiastic participants in research studies, are probably the most valuable resource in the world for identifying these genes. Palestinian kindreds K, Y, C, and J are extended families, unrelated to each other, with congenital deafness in multiple generations. The deaf persons and their informative relatives in these families are already participants in this study, with genealogical information, clinical histories, and DNA obtained with informed consent of each person. Dr. Kanaan spent the past 8 months as a Fulbright Visiting Professor in the King lab, where he evaluated these families by current genomic approaches. Using genome-wide linkage analysis, Dr. Kanaan mapped hearing impairment in Family K to a 5.4 cM region of chromosome 22q13; the new locus has been named DFNB28. He identified multiple candidate genes in this region, excluded two by sequence analysis of the family, and showed that this region is not linked to deafness in families Y, C, or J. He excluded all known genes for inherited deafness in these families, demonstrating that these kindreds represent new, previously unknown genes for inherited hearing loss. Our goals for this FIRCA are (1) to complete fine mapping of hereditary hearing impairment with additional relatives of Family K, then clone this gene for hereditary hearing impairment; (2) to map the different genes responsible for hereditary hearing impairment in Families C, Y, and J; and (3) to identify additional extended Palestinian families with hereditary hearing impairment. This FIRCA is collaborative with the existing FIRCA between M-C King and Karen Avraham of Tel Aviv University. The ultimate goal of our three-way collaboration is to transfer the technology for identification of genes for important human conditions to Middle Eastern geneticists.